The Immunobiology Program aims to: 1) Understand the fundamental aspects of immune biology, including activation, differentiation, inactivation, and transformation as these relate to cancer; 2) Forge a comprehensive understanding of tumor immune surveillance using state-of-the art in vitro, animal model, and human experimental systems; and 3) Translate novel clinical strategies for immunotherapy of cancer by the design, implementation, and analysis of proof-of-concept human clinical trials. Established in 1974, this Research Program received Outstanding merit at the time of the last CCSG renewal application. The Program is Co-Led by Robert Vonderheide, MD, DPhil, an expert in tumor immunology and immunotherapy, and Warren Pear, MD, PhD, an expert in the molecular biology of leukocyte development and malignant transformation. Drs. Vonderheide and Pear are experienced, NCI-funded investigators who are highly collaborative and whose research interests span the realm of basic and translational science. There are 34 Program members from 10 departments and four schools with long-standing intra- and inter-Programmatic collaborations spanning the Basic as well as Clinical Programs. Through these interactions, the members' collective expertise serves as a rich resource for the pursuit of interdisciplinary approaches to fundamental questions about the immunobiology and immunotherapy of cancer. Members include national leaders in basic immunology, tumor immunobiology and translational immunotherapy. The Program Co-Leaders facilitate interactions through multiple weekly seminars and meetings, promotion of collaborative grants and projects, an annual research retreat, Pilot Project grants, and training programs. During the current project period, Program Leaders recruited new members, expanded important forums, facilitated new collaborative grants, initiated new ACC-wide initiatives, and were actively involved in decisions regarding new and existing Shared Resources. Currently, Program members have $20.6M in research grant funding (annual direct costs), of which $11.3M is peer-reviewed and $2.2M is NCI-funded. During the current project period, Program members published 421 cancer-related publications, many of which are in top journals in the field. Of these, 17% are intra-Programmatic, 24% are inter-Programmatic, and 29% are multi-institutional.